| Lung transplantation is actually considered as an effective therapy in end-staged pulmonary disease. Compared with the heart, liver, or kidney transplantation, its morbidity and mortality remained high, however. Ischemia-reperfusion-induced lung injury has been identified as the main cause of primary graft failure and mortality after lung transplantation, its prevention and treatment can be anticipated with much more success. In addition, the donor lung is still rather scanty because the ischemic time provided by preservation technique available at present is limited. It is therefore necessary to explore and improve the technique of donor lung preservation.Constitutive expression of endogenous nitric oxide (NO) by the pulmonary vascular endothelium plays an important role in maintaining the homeostasis in many aspects of the pulmonary circulation, including modulation of pulmonary vascular tone, maintenance of an intact pulmonary capillary membrane, inhibition of platelet aggregation and leukocyte adhesion. A marked decrease of endogenous NO has been found during lung transplantation. Previous studies have demonstrated that administration of NO or NO donors may greatly improve the function of heart and liver after transplantation.We used a canine single lung transplantation model to evaluate the protective benefits of L-Arginine (L-Arg), a substrate of endogenous nitric oxide synthesis, to the isolated donor lung or toischemia-reperfusion-induced injury lung by adding L-Arg as an additive to the cooling preservation and flush EC solution. Moreover, we tried to explore the possible mechanisms.Part 1 Effect of L-Arg on isolated donor lung preservation1.1 Objective: To investigate the protective effect of L-Arg on the preservation of isolated donor lung and the possible mechanisms based on a canine single lung transplantation model.1.2 Methods: Ten dogs were randomly divided into 2 groups. In the control group, the isolated donor lungs were flushed with and preserved in cold Euro-collins solution(EC) at 4 C . In the experimental group, the isolated donor lungs were flushed with and preserved in cold EC added with 2g/L L-Arg at 4 C. After preservation for 30, 60, 120, 180, 240min respectively, the tissue samples of donor lung were subsequently obtained for the measurement of nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) contents. In addition, the wet to dry weight ratio (W/D) and histological changes were also observed at 240min.1.3 Results: The comparison of control and experimental groups revealed that there were significant differences in NO, SOD, MDA contents and W/D at any appointed time points (P<0.05, P<0.01). The NO and SOD contents of experimental groups were significantly higher than that of the control group. But the MDA contents were lower in the experimental group. Furthermore, The NO and SOD contents tended to drop while MDA level rose as the duration of preservation was lengthened. These phenomena were more prominent in the control group. The W/D and light microscope revealed that the control group was more seriously damaged (P<0.05).1.4 Conclusion: L-Arg added in EC has a significant protective effect in isolated donor lung preservation. The increased NO production and changes of the balance between clearout andproduction of oxygen-free radicals are likely the main mechanisms.Part 2 Effect of L-Arg on ischemia-reperfusion injury in lung transplantation2.1 Objective: To investigate the protective effect of L-Arg on ischemia-reperfusion injury in lung transplantation and possible mechanisms based on a canine single lung transplantation model.2.2 Methods: Sixteen dogs were randomly divided into 2 groups. In the control group, the donor lungs were flushed with and preserved in the cold EC at 4C. In the experimental group, the donor lungs were flushed with and preserved in cold EC added with 2g/L L-Arg at 4C. After 4 h preservation, the left lungs were implanted into...
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